Abstract 17504: Time-dependent Association of Circulating microRNAs With Death and Myocardial Infarction After Non-ST Elevation Acute Coronary Syndrome
Background: Clinical risk scores for risk stratification of non-ST elevation acute coronary syndrome (NSTE-ACS) accurately predict death but not myocardial infarction (MI) events. Circulating microRNAs (miRs) have emerged as promising biomarkers of cardiovascular disease. We investigated the temporal association of circulating miRs with death and MI events in NSTE-ACS.
Methods: Forty candidate miRs were measured by real-time PCR in plasma from 1041 patients in the TRILOGY-ACS trial, during the initial ACS (N=1041) and 30 days later (N=748). The association between miRs and time to MI or death was tested in a Cox model adjusted for clinical risk factors. A hazard ratio <1 and >1 indicate a reduced risk and increased risk, respectively, of death or MI with increasing miR expression.
Results: Over a median of 24 (range 18-30) months, 90 MIs and 67 deaths occurred. Four miRs measured at baseline (miR-15b, 20a, 20b and 29c) and 15 miRs measured at 30 days (miR-1, 22, 25, 30a, 92a, 92b, 134, 192, 208a, 222, 296, 484, 574, 636, 6087) were nominally associated with MI events. Four miRs measured at baseline (miR-29a, 126, 134 and 296) and four miRs measured at 30-days (miR-15b, 19b, 21 and 126) were nominally associated with death. The miRs most significantly associated with MI (P<0.01) included miR-20a, 20b and 92a, which are members of the miR17/92 cluster regulating cell death and differentiation. The miR most significantly associated with death (P<0.01) was miR 29a-3p, which regulates cardiac fibrosis after ischemic injury. The association of four out of five top miRs with MI, namely miR-22, 25, 92a and 484, was not apparent at baseline measurements but emerged strongly at 30-day measurements (table).
Conclusion: Specific plasma miRs are differentially associated with death or MI events in a time-dependent fashion, suggesting that risk stratification of NSTEACS with circulating miR profiles requires a miR-specific and time-sensitive approach.
Author Disclosures: M.Y. Chan: Research Grant; Significant; Eli-Lilly, Astra-Zeneca, Bayer Healthcare. Speakers Bureau; Modest; Astra Zeneca. M.L. Neely: None. L. Kwee: None. K.A. Fox: Research Grant; Significant; Bayer/Janssen, AstraZeneca. Honoraria; Modest; Bayer, AstraZeneca, GlaxoSmithKline, Janssen, Sanofi. Consultant/Advisory Board; Modest; Bayer, Lilly, AstraZeneca, Sanofi. E. Burns: None. S. Gregory: None. P. Armstrong: Research Grant; Significant; Merck, AstraZeneca. Consultant/Advisory Board; Modest; Merck. Other; Modest; Merck. E. Ohman: Research Grant; Significant; Daichii Sankyo. Honoraria; Modest; Astra Zeneca. H. White: Research Grant; Significant; Sanofi, Eli Lilly, MSD. Honoraria; Modest; Astra Zeneca. M.T. Roe: Research Grant; Significant; Eli-Lilly, Astra-Zeneca. Honoraria; Modest; Astra Zeneca, Eli Lilly. S. Shah: None.
- © 2016 by American Heart Association, Inc.